Smoking-related outcomes vary by gender. Compared to men, women more rapidly increase their cigarette consumption after they begin smoking, have more difficulty discontinuing their use once they become dependent, and respond more poorly to smoking cessation treatments involving exclusively nicotine replacement therapy. Social, cultural, and biological factors likely interact to contribute to gender differences in smoking outcomes. However, studies demonstrating differences in smoking cessation outcomes across the menstrual cycle, as well as animal research implicating a role for ovarian hormones in nicotine-related reinforcement, suggest that hormonal mechanisms may be paramount. Ovarian hormones have been shown to affect sensitivity to both drug- and non-drug-related reinforcement via interactions with the dopaminergically mediated reward-processing system, and alterations in this system are implicated in nicotine dependence as well as a range of other psychiatric disorders. Despite the potential relevance to understanding gender differences in smoking outcomes, the role of ovarian hormones in sensitivity to the reinforcement of cigarette smoking has not been studied. The overall goal of this investigation is to systematically examine the effects of menstrual phase on the positive and negative reinforcing effects of cigarettes in female smokers. We will recruit 40 healthy female smokers between the ages of 18 and 45 to participate in a repeated measures research design. A Progressive Ratio (PR) task will be used to measure smoking reinforcement;cotinine, estrogen, and progesterone levels will be measured to verify smoking status and menstrual cycle phase;and mood, smoking behavior, and subjective experience of smoking will be examined using self-report measures. Specific aims include the following: 1) to characterize the role of menstrual phase on the behaviorally reinforcing effects of cigarettes in female smokers using a PR task;2) to characterize the role of menstrual phase on the subjectively reinforcing effects of cigarettes in female smokers using self-report measures;and 3) to examine the relationship of menstrual cycle-related fluctuations in estrogen levels, progesterone levels, and estrogen/progesterone ratios on the behaviorally and subjectively reinforcing effects of cigarettes. This project will serve as a pilot study to determine the feasibility and relevance of a larger study examining potential hormonal mechanisms of gender differences in smoking outcomes and their relevance to treatment. The results may contribute to the development of novel treatments tailored to address the unique behavioral and physiological needs of female smokers, particularly those who suffer from comorbid psychopathology associated with dysreguation of reinforcement processes. PUBLIC HEALTH RELEVANCE: Compared to men, women more rapidly increase their cigarette consumption after they begin smoking, have more difficulty discontinuing their use once they become dependent, and respond more poorly to smoking cessation treatments involving exclusively nicotine replacement therapy. This research project is designed to improve understanding of mechanisms associated with increased cigarette smoking in women, thereby addressing a significant health issue that is relevant to a large segment of the population.